The needle and the damage done

PUBLISHED : Sunday, 24 February, 2008, 12:00am
UPDATED : Sunday, 24 February, 2008, 12:00am

Pu Mengqi was just one month away from graduation at college in Suzhou - 50km inland from Shanghai - when she was diagnosed with leukaemia, in May 2006. She underwent the first round of treatment before moving to Beijing with her parents for better care at the capital's prestigious Daopei Hospital. Chemotherapy made her lose her hair and appetite but doctors said her chances of recovery were good. Then, on June 28 last year, she was given a spinal injection of tainted medicine that caused her to lose control of her legs, her bladder and her bowels. Unlike her hair and appetite, that control will never return.

Pu is just one victim of what is emerging as one of China's worst reported medical scandals. Over a period of two months last summer, nearly 200 leukaemia patients were treated with an anti-cancer drug contaminated during manufacture at a subsidiary of one of the country's biggest pharmaceutical groups. This number would have been much smaller were it not for an attempted cover-up by managers at the firm, Shanghai Hualian Pharmaceutical. All the victims have lost the ability to walk normally. Most are paralysed from the waist down. Once the media coverage has subsided, they will probably be forgotten; poorly compensated, they will struggle through a life of destitution and disability.

The affair is a painful reminder of how far the mainland is from building a system that can ensure the safety of the medicine it makes and supplies. In several cases over the past few years, scores of people in China and abroad have had their health damaged - often fatally - by using drugs and drug ingredients produced on the mainland. Last July, the seriousness of the situation was underlined by the execution of a former food and drug regulator. Zheng Xiaoyu had been found guilty of taking bribes from pharmaceutical companies, when head of the State Food and Drug Administration (SFDA), in return for granting licences to supply medicines to mainland clinics and hospitals.

Ironically, it was just as Zheng was being put to death that Shanghai Hualian's poisoned drugs started to take effect. The company is part of the giant state-owned Shanghai Pharmaceutical Group, which has supplied ingredients to, or set up joint ventures with, foreign multinationals, including Swiss-based Roche. In addition to anti-cancer drugs, Hualian produces hormones and pharmaceuticals used in birth control at three plants around Shanghai. These are sold domestically and exported to 70 countries, according to the company website. Many are sold under the brand name Sanjian, which means 'triple health'.

A search of the Department of Health's database found that no pharmaceuticals supplied by either Shanghai Hualian or Shanghai Pharmaceutical Group are registered for sale in Hong Kong. Neither company responded to requests for an interview from Post Magazine.

FROM HER HOSPITAL room in the west of Beijing, Pu, now 22, tells of her life-destroying encounter with the chemotherapy drug methotrexate. The ward has been her home since shortly after she was injected. Evening sunlight seeps into the dingy room, illuminating her smooth, hairless head and the wall behind. Beside her bed, a bag of lychees and a flask of oolong tea sit on top of a grey metal cabinet.

Pu was an outpatient preparing for a bone-marrow transplant at the time: therapy that offered a good chance of curing her leukaemia. Her parents, retired farmers, had sold the family house to pay for it. A suitable donor was found after months of searching. The transfusion was then set for an auspicious date: August 8, a year to the day before the Beijing Olympic Games would open.

About a week after the contaminated injection, Pu was out walking when she felt numbness in her legs. 'I found myself having to squat after every few paces,' she recalls. Some days later, Pu had no control over her legs and had become incontinent. On July 9 she developed a fever. 'All I could do was lie rigid on my bed. I couldn't even turn myself over,' she says. 'My whole body was in complete agony.'

Doctors at the Daopei Hospital subjected Pu to a battery of tests, the results of which were all negative. One doctor suggested the medicine as a cause but this made no sense. Methotrexate's side effects include nausea, hair loss and even temporary difficulty with walking but never complete lower-body paralysis.

By this time, however, reports were coming in from hospitals in Shanghai and Guangxi. Similar symptoms were appearing in patients there after injections of Shanghai Hualian's methotrexate. Patients treated with another anti-cancer drug, cytarabine hydrochloride - made at the same factory - were also suffering. The SFDA had ordered a nationwide stop to the use of methotrexate on July 7.

According to a report in Guangzhou newspaper Southern Weekly, officers were despatched from Beijing to assist colleagues from the Shanghai municipal FDA in an investigation of the factory making the drug. Yet interviews with the plant's managers and an inspection of records yielded nothing, so the stoppage order was lifted.

It was only after two further probes, in which local FDA officers were replaced by police and all officers warned to be sceptical of information they received, that SFDA workers uncovered the truth. Shanghai Hualian's methotrexate had been mixed during production with another anti-cancer drug - vincristine sulfate, a drug too toxic for injection.

After the SFDA had lifted its stoppage order, many more leukaemia sufferers had been injected with tainted methotrexate.

Zhang Yujin is one of them. The 29-year-old Beijing hotel worker had been married for just one month when he was diagnosed with leukaemia in December 2006. 'It was a shock but I made the psychological adjustment,' he says. 'The doctors said my chances of complete recovery were good. I had a loving wife and my whole life ahead of me. But then came disaster.'

Zhang languishes in a room in the China-Japan Friendship Hospital, in the capital's northeast. A saline drip is attached to one arm. His withered legs are stretched out, skinny and useless. His belongings are packed into boxes under the metal frame of the bed.

His fateful injection was administered on July 17, 10 days after the SFDA's first investigation. He recalls feeling numbness a few days later. Then came the horrifying deterioration into complete paralysis and loss of bladder and bowel control.

Since then, Zhang says, he has spent 400,000 yuan on in-patient care, for both leukaemia and his new condition of paraplegia. This is equal to about 15 years' wages in his old job. He raised it by borrowing from family, friends and workmates, as well as by selling his belongings.

'This money wouldn't matter if I could just use my legs again,' he says. 'To begin with, I thought I could make them move by sheer force of will. But now ... I've given up and it's clear my whole life is going to be a fight against this. How can I go on?'

Not until September 5 did the SFDA issue a second stoppage order, covering all methotrexate and cytarabine hydrochloride produced by Shanghai Hualian. A week later, Xinhua reported a nationwide recall, citing a statement by the National Centre for Adverse Drug Reaction Monitoring that 'several' leukaemia patients injected with methotrexate had 'felt pain in their legs' and experienced 'difficulty in walking'. In December, the SFDA accused Shanghai Hualian managers of a 'systematic cover-up'. Media coverage intensified and the full scale of the tragedy began to emerge. According to the Southern Weekly, there have been 193 victims nationwide.

Zhou Baoqin has led a support group in Beijing since his 20-year-old daughter was injected with the tainted drug at Beijing's 307 People's Liberation Army Hospital on June 29. He says there are 53 victims in the capital alone. Seventy per cent, he reckons, cannot walk at all.

The SFDA has not published findings from its investigation but, on January 17, Southern Weekly reported the agency had found five procedural failings at Shanghai Hualian. One involved a single production line that had been used to produce more than one drug, creating the risk of cross-contamination. Another was the failure to throw out ingredients left over from one batch of drugs and their being used in another batch of the same drug.

Even now, it's not completely clear what went wrong. 'These [departures from protocol] don't necessary violate good manufacturing practice. Leftover ingredients can be stored properly and a production line can be thoroughly cleaned between batches of different drugs,' says Zheng Qiang, director of the Centre for Pharmaceutical Information and Engineering Research at the capital's Peking University. 'The only violation we can be sure of is that workers at Shanghai Hualian lied to SFDA investigators.'

The FDA in Shanghai has revoked Shanghai Hualian's licence to produce anti-cancer drugs and fined the company a total of 1.24 million yuan. Whether or not these sanctions constitute an effective deterrent, the most positive consequence could come through coverage by foreign media. Reports of the case in The New York Times and The Wall Street Journal focused on potential dangers to consumers in the US from Shanghai Pharmaceutical Group's products. This has jeopardised exports to a vital market and the mainland drugs industry will surely take heed. International coverage was made possible by largely unfettered domestic reporting. This is in line with the mainland government's avowed policy of 'openness and transparency', and would have been unthinkable 10 years ago.

But what about Shanghai Hualian's victims?

Only one of the many mainland doctors approached was willing to comment. The head of the China-Japan Friendship Hospital's intensive care unit, Dr Li Gang, says that, although up to half of leukaemia patients will lose their fight against the disease anyway, the chances of recovery of those treated with polluted methotrexate have been reduced by the additional strain on their health.

Retired factory worker Li Zhizhong, for example, was 69 when, in November last year, he died of kidney failure, having been crippled by the tainted drug in the summer. His daughter, Li Gang, reckons this was caused by repeated bladder infections contracted after he became incontinent. 'After he lost the ability to stand up on his own, he lost the will to live,' she says.

Bone-marrow transplant recipients must be completely germ-free before they enter a special antiseptic isolation unit prior to the procedure. After Pu was made an invalid, she became incontinent and was dogged by repeated infections. This led her doctors to decide a transplant was no longer an option.

In January, Shanghai Hualian distributed compensation 'contracts' to each of the families of its victims. These offer a single payment of between 200,000 and 700,000 yuan. Those who are young and those living in urban areas have been offered more than older and rural-dwelling sufferers. The contracts make it clear this payment will be final. If they accept, patients must leave hospital and return home. They must not give interviews to the media.

Given that all the families interviewed say they have already spent well over half the amount they have been offered on treatment, it's not surprising most have refused to sign. Zhou says that in Beijing, only 18 have done so. In most of these cases, he says, the victim is approaching death or has already passed away.

'These people are like gangsters,' says Pu's father, Pu Huijiang. 'They know the longer they drag this out, the higher the number of victims who will have died. Either that, or the families will ... have sold everything they have. They'll have no money left to pay for treatment so they will be forced to accept.'

Chen Beiyuan, the Guangzhou lawyer representing the victims and their families, is remaining tight-lipped. 'I can't talk to foreign media about this,' he says. 'It's against national regulations.'

At the China University of Political Science and Law, in Beijing, however, Professor Wu Jingming points out that damages granted in the mainland for cases such as these are much lower than those in developed countries. In March last year, for example, 10 patients in Guangzhou sued the city's No 3 Zhongshan Hospital for a combined 20 million yuan after they were treated with counterfeit antibiotics and developed acute kidney failure. By the time the last of them had died, in January, the court handling the case had not reached a verdict. In Jiangxi province, the family of a victim of the same fake drug eventually accepted damages of 109,000 yuan.

'If the families took Shanghai Hualian to court, there would be expensive legal fees and the case could drag on for a very long time,' says Wu. 'Even then, they'd be unlikely to win a better deal than the one already on offer.'

That leaves the victims of the company's blunder facing a struggle against poverty as well as disability. Given the mainland's lack of facilities for the disabled and their exclusion from public life, most of their suffering will probably take place alone at home.

As the light fails in Beijing's winter sky, Zhou sits at the bedside of his daughter, Xue, at the PLA hospital. She uses her arms to drag her body to the side of the bed, before toppling forwards and leaning on her father for support.

'You see what they've done to her?' he says. 'Nobody has been injected with these chemicals before. Nobody knows how to treat her or how her condition will develop.'